Long non-coding RNAs (lncRNAs) are pervasively transcribed in the genome. They have important regulatory functions in chromatin remodeling and gene expression. Dysregulated lncRNAs have been studied in cancers, but their role in esophageal squamous cell carcinoma (ESCC) remains largely unknown. We have conducted lncRNA expression screening and a genome-wide analysis of lncRNA and coding gene expression on primary tumor and adjacent normal tissue from four ESCC patients, tend to understand the functionality of lncRNAs in carcinogenesis of esopheagus in combination with experimental and bioinformatics approach. LncRNA array was used for coding and non-coding RNA expression. R program and Bioconductor packages (limma and RedeR) were used for differential expression and co-expression network analysis, followed by independent confirmation and functional studies of inferred onco-lncRNA ESCCAL-1 using quantitative real time polymerase chain reaction, small interfering RNA-mediated knockdown, apoptosis and invasion assays in vitro. The global coding and lncRNA gene expression pattern is able to distinguish ESCC from adjacent normal tissue. The co-expression network from differentially expressed coding and lncRNA genes in ESCC was constructed, and the lncRNA function may be inferred from the co-expression network. LncRNA ESCCAL-1 is such an example as a predicted novel onco-lncRNA, and it is overexpressed in 65% of an independent ESCC patient cohort (n = 26). More over, knockdown of ESCCAL-1 expression increases esophageal cancer cell apoptosis and reduces the invasion in vitro. Our study uncovered the landscape of ESCC-associated lncRNAs. The systematic analysis of coding and lncRNAs co-expression network increases our understanding of lncRNAs in biological network. ESCCAL-1 is a novel putative onco-lncRNA in esophageal cancer development.

Purpose: Studies have shown that eye rubbing is associated with increased risk of keratoconus (KC). However, the potential mediating roles between eye rubbing and KC remain largely unknown. Hence, this study aims to explore the mediating roles of two specific factors, namely, the inverse of the stiffness parameter at the first applanation (-SPA1) and maximal corneal keratometry (Kmax) values, in the relationship between eye rubbing and KC.Methods: A total of 395 patients with KC and 396 controls from the Chinese keratoconus (CKC) cohort study were included in this case–control analysis. The Spearman correlation and generalized linear regression models were used to analyze the associations between the time of eye rubbing, -SPA1, Kmax, and KC. Furthermore, three mediation models (individual, parallel multiple, and serial multiple) were utilized to investigate the mediating roles of -SPA1 and Kmax in the relationship between eye rubbing and KC.Results: After adjusting for confounding factors, the odds ratio and 95% confidence interval (CI) for the time of eye rubbing, -SPA1, and Kmax in relation to KC were 1.02 (1.01, 1.04), 1.16 (1.12, 1.19), and 3.86 (2.52, 5.92), respectively. The individual mediation model indicated that the indirect effects of -SPA1 and Kmax were 0.084 and 0.056, respectively. The parallel multiple mediation model showed a total indirect effect of 0.081 for -SPA1 and Kmax. Additionally, the serial multiple mediation model (time of eye rubbing → -SPA1 → Kmax → KC) indicated that following -SPA1, Kmax partially mediated the relationship between the time of eye rubbing and KC with a total indirect effect of 0.024 (95% CI: 0.016–0.042), accounting for 14.5% of the total effect (time of eye rubbing on KC), while no significant indirect effect was found for Kmax alone.Conclusions: The individual, parallel multiple, and serial multiple mediation analyses consistently demonstrated the mediating roles of -SPA1 and Kmax in linking the duration of eye rubbing to KC. Notably, the serial mediation pathway (time of eye rubbing → -SPA1 → Kmax → KC) exhibited a significant indirect effect. These findings confirm and complement the theoretical framework linking eye rubbing to KC, providing a reference for further exploration of the pathogenesis of KC.

Background: The gut microbiota in patients with Graves’ orbitopathy (GO) may influence the disease’s progression, but its specific role and function in the progression of GO treatment are not well understood. Methods: We performed fecal microbiota sequencing using the 16S rRNA-gene sequencing on patients with GO ( n = 48), Graves’ disease (GD, n = 40), and healthy controls (HC, n = 36). Subsequently, fecal samples from patients with GO, GD, and healthy donors were transplanted into antibiotic-treated pseudo-germ-free mice. Finally, the 48 patients with GO were randomly divided into two groups: one group received intravenous glucocorticoids (ivGC) and atorvastatin ( n = 24), while the other group received ivGC only ( n = 24), to observe the effects of atorvastatin on GO progression and its impact on gut microbiota. Results: Patients with GO exhibit a distinct gut microbiota composition, particularly marked by increased levels of Prevotella and Bacteroides , compared to patients with GD and HC. Correlation analysis revealed a direct positive association between Prevotella and thyrotropin receptor antibody levels. Antibiotic-treated pseudo-germ-free mice that received fecal transplants from patients with GO exhibited a slower rate of weight gain, significant impairment of intestinal barrier integrity, and markedly increased levels of serum LBP and inflammatory factors. A combined treatment regimen of ivGCs and atorvastatin significantly reduced ocular clinical symptoms in patients with GO, including clinical activity score, exophthalmos, and intraocular pressure, while also promoting a healthier gut microbiota composition and a reduction in Prevotella levels. Conclusions: Gut microbiota imbalance, particularly involving Prevotella , contributes to GO’s development and progression. Atorvastatin may slow GO progression by correcting dysregulated gut microbiota, especially reducing Prevotella .

Keratoconus (KC) is a corneal disorder characterized by progressive corneal protrusion and thinning. Our previous studies have demonstrated that genetic factors influence KC occurrence. The purpose of this study was to explore the genetic model of KC from the perspective of genetic epidemiology. A total of 157 KC families, including 157 KC probands and their 445 first-degree relatives, from the Chinese Keratoconus (CKC) Cohort Study were included in present study. The genetic model of KC was evaluated by three genetic epidemiological analyses, including the Penrose method, simple segregation analysis, and complex segregation analysis, where the complex segregation analysis was conducted using the Statistical Analysis for Genetic Epidemiology package. The 157 KC families included 181 affected individuals, 384 unaffected individuals, and 37 unknown individuals. There are 24 individuals diagnosed with KC among the 445 first-degree relatives. The relative frequency calculated by the Penrose method was 33.188, which was close to 1/√q. In addition, the segregation ratio calculated by the simple segregation analysis was 0.046, which was less than 1/4. Furthermore, all the hypotheses of Mendelian, nontransmission and environmental model were rejected by complex segregation analysis. These results fully showed that KC is a disease of multifactorial inheritance. This study identified that KC followed a pattern of multifactorial inheritance, which is helpful to provide initial guidance for prevention and management of the disease and points out a research direction for future research.

Introduction: The clinical biochemical characteristics and target organ damage (TOD) in patients with plasma aldosterone concentrations (PAC) ranging from 50 to 100 ng/L after a saline infusion test (SIT) have not been fully studied.Methods: A total of 611 hypertensive patients with an elevated aldosterone-to-renin ratio (ARR) who underwent a supine SIT at Henan Provincial People’s Hospital were enrolled. The patients were divided into three groups according to their post-SIT PAC: 100 ng/L (PA group). The clinical and biochemical characteristics and TOD of the three groups were compared. The correlation of the post-SIT PAC with left ventricular mass index (LVMI) was assessed via regression analysis.Results: The indeterminate post-SIT results group had the youngest patients and the shortest duration of hypertension. The prevalence of renal impairment (RI) and left ventricular hypertrophy (LVH) was lower than that in the PA group (P0.05). After adjustment for confounders, the risk of developing carotid plaque was greater in the indeterminate post-SIT results group than in the control group (OR 1.73, 95% CI: 1.11, 2.69), and the prevalence of RI and LVH tended to increase with increasing post-SIT PAC levels. In multiple regression analyses, LVMI was significantly correlated with post-SIT PAC (P0.05).Conclusion: A post-SIT PAC of 50–100 ng/L may be indicative of an early form of PA, and it may serve as an independent predictor of LVH, which could be related to the level of autonomously secreted aldosterone.